José Baselga, MD, PhD

2012-2013 BCRF Project:
Recent advances in the therapy of HER2 positive (HER2+) tumors include the clinical activity of new anti-HER2 agents in patients resistant to trastuzumab (Herceptin®), and the observation that dual HER2 blockade (the combined administration of anti-HER2 agents with partially non-overlapping mechanisms of action) may be superior to single agent anti-HER2 therapy. While these new agents and approaches are promising, the eventual development of clinical resistance remains a significant problem. The main aims of Dr. Baselga's research are to discover new mechanisms of resistance to anti-HER2 therapy (trastuzumab or Herceptin® and lapatinib or Tykerb®) and to study the combinations of new agents that counteract the insurgence of such resistance.

Thanks to the establishment and characterization of novel preclinical models of anti-HER2 resistance, Dr. Baselga and his team have identified a number of genes that may be involved in reducing the anti-tumoral effects of trastuzumab, lapatinib or the combination of both. Importantly, they have also started the collection and analysis of samples from HER2+ breast cancer patients who initially responded but eventually relapsed on anti-HER2 therapy. Data obtained from these specimens will be matched with their laboratory findings, aiming to uncover genuine and clinically relevant mechanisms of anti-HER2 resistance.

Moreover, Dr. Baselga's team has demonstrated that PI3K inhibition, together with lapatinib, has very promising anti-tumor activity in tumors intrinsically resistant to anti-HER2 therapy, without signs of significant toxicity. This finding was published in 2012 in the Clinical Cancer Research journal. This research will help to advance understanding aimed at better and safer ways to prevent, delay or overcome the insurgence of resistance to anti-HER2 therapy.

Mid-year Progress: Dr. Baselga's team has made significant progress towards the validation of their three main hypotheses. In breast cancer models that express hormone receptors, they found that combinations of PI3K inhibitors with either anti-estrogen agents or an inhibitor of mTORC1 result in profound antitumor activity. Moreover, in those models of breast cancer that do not depend on hormone receptor for their survival, the investigators have confirmed that inhibiting EGFR, HER3 and PI3K concomitantly is safe and efficacious in preventing tumor growth. They are confident that their ongoing studies will confirm these positive results and be instrumental for the design of novel clinical trials for these subgroups of breast cancer patients.

Bio:
José Baselga, MD, PhD has published over 300 peer-reviewed articles, in addition to over 400 abstracts and book chapters. His research interests are in Clinical Breast Cancer and in Translational and Early Clinical Research in the area of Growth Factor Receptors and Downstream Molecules as Targets for Breast Cancer Therapy. He conducted the initial clinical trials with the monoclonal antibodies cetuximab and trastuzumab. In addition, he has been involved in the clinical development of several new agents including: gefitinib, erlotinib, lapatinib, pertuzumab, m-TOR, PI3K, TGF, SRC, Insulin-like Growth Factor Receptor Inhibitors and a variety of anti-angiogenic agents. His main focus in the laboratory and in the clinic is the area of novel anti-HER2 agents, in the identification of mechanisms of resistance to anti-HER2 agents and therapeutic approaches to target the PI3K pathway.

Dr. Baselga served as President of the European Society of Medical Oncology (ESMO) in 2008-2009. He is a member of several Committees of the American Association for Cancer Research (AACR) and a member of the AACR Research Council and the AACR Board of Directors; a past member of the Board of Directors of the American Society of Clinical Oncology (ASCO), a past member of the Board of Directors of the European Organization of Research on Treatment of Cancer (EORTC); and a member of the Scientific Advisory Committee of the Ludwig Institute for Cancer Research.

Dr. Baselga has received a number of awards including a Young Investigator Award from ASCO (1992), a Career Development Award from ASCO (1994), a Brystol-Myers Squibb Unrestricted Cancer Grant Award (2002-2006), an Honorary Membership Award from The European Society for Therapeutic Radiology and Oncology (ESTRO) (2004); the Waun Ki Hong Visiting Professorship at U.T.M.D. Anderson Cancer Center in Houston, TX (2002); named Distinguished Alumnus from Memorial Sloan Kettering Cancer Center, NY (2004); Elected Member of the American Society of Clinical Investigation (2004); Annual Award from ESMO (2005); American- Italian Cancer Foundation (AICF) Prize for Scientific Excellence in Medicine (2007); AACR-Rosenthal Family Foundation Award (2008); and King James I Award (2008)

Dr. Baselga received his medical degree from the Universidad Autonoma of Barcelona in 1982. He did his Internal Medicine Residency at both Vall d'Hebron University Hospital in Barcelona, Spain and the State University of New York in the US. He completed a fellowship in Medical Oncology at Memorial Sloan-Kettering Cancer Center in New York and subsequently stayed on as a faculty member of the Breast Medicine Service at Memorial Sloan-Kettering until 1996 when he returned to Spain.

From 2010-2012, Dr. Baselga was Chief and Bruce A. Chabner Chair of the Division of Hematology/Oncology at Massachusetts General Hospital (MGH), Associate Director of the MGH Cancer Center, and Professor of Medicine at Harvard Medical School. In 2011, Dr. Baselga was also appointed Associate Director of Clinical Services at Dana-Farber/Harvard Cancer Center.

Prior to MGH, Dr. Baselga was the chairman of the Medical Oncology Service and the founding director of the Vall d'Hebron Institute of Oncology established in 2007 at the Vall d'Hebron University Hospital in Barcelona, Spain. He was also a Professor of Medicine at the Universidad Autonoma de Barcelona. Dr. Baselga holds the position of Scientific Chairman of SOLTI, the Spanish Breast Cancer Cooperative Group. He is a member of the Editorial Boards of Cancer Cell, Journal of Clinical Oncology, Clinical Cancer Research, and Annals of Oncology.

In September 2012, Dr. Baselga was named Physician-in-Chief of Memorial Hospital, part of Memorial Sloan-Kettering Cancer Center (MSKCC) in New York, and will direct the clinical component of MSKCC and lead its team of 834 attending physicians.